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MDM-2 protein is expressed in different layers of normal human skin
1Institut de Génétique Moléculaire, UMR 5535, Montpellier, France.
Abstract:
MDM-2 is one of the target genes of the p53 tumor suppressor protein. Its best characterized function is found in the inhibition of p53's ability to modulate transcription. Deregulated expression of MDM-2 could thus at least partially substitute for p53 mutation in the process of tumorigenesis. We show here that MDM-2 is highly expressed in biopsies of normal human skin or in vitro reconstituted human skin. The protein is detected in the nucleus of keratinocytes throughout the different layers of the epidermis and in reconstituted skin as early as the two to three cell layer stage. The 90 kiloDalton (kD) protein is one of the major forms detected in Western blot experiments. MDM-2 is detected in skin reconstituted from keratinocytes in which p53 is inactivated by mutation or degradation by E6 protein, providing evidence that MDM-2 expression in the skin can occur in the absence of wild type p53. Moreover, we found no correlation between the p53 status and MDM-2 expression levels in a series of basal and squamous cell carcinomas or Bowen diseases. Our data provide first evidence for the expression of MDM-2 in a differentiated adult tissue.
Insights
MDM-2 protein is highly expressed in normal human skin, independent of p53 status. This finding suggests MDM-2 plays a role in skin biology, even when p53 is altered, potentially contributing to tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- MDM-2 is a target gene of the p53 tumor suppressor.
- MDM-2 inhibits p53's transcriptional modulation.
- Deregulated MDM-2 expression may contribute to tumorigenesis.
Purpose of the Study:
- To investigate MDM-2 expression in normal human skin.
- To determine if MDM-2 expression correlates with p53 status in skin cancers.
Main Methods:
- Western blot analysis of MDM-2 protein.
- Immunohistochemical detection in skin biopsies and in vitro reconstituted skin.
- Analysis of skin cancers (basal cell carcinoma, squamous cell carcinoma, Bowen disease).
Main Results:
- MDM-2 is highly expressed in normal human epidermis and in vitro reconstituted skin.
- MDM-2 is detected in keratinocyte nuclei across epidermal layers.
- MDM-2 expression occurs independently of wild-type p53 and shows no correlation with p53 status in skin carcinomas.
Conclusions:
- MDM-2 is expressed in differentiated adult human skin.
- MDM-2 expression in skin is not dependent on wild-type p53.
- MDM-2 may play a role in skin biology and tumorigenesis, irrespective of p53.
- This study provides the first evidence of MDM-2 expression in differentiated adult tissue.